Human AQP5 plays a role in the progression of chronic myelogenous leukemia (CML).

Young Kwang Chae,Inho Kim,Jiyoung Rhee,David Sidransky,Myoung Sook Kim,Nam Hee Koo,Se-Eun Jang,Juna Lee,Janghee Woo,Gyeongsin Park,Bhumsuk Keam,Myungshin Kim,Sung Koo Kang,Chulso Moon,Dong Wook Kim ,Il Young Kweon ,Steven S Chang ,Sang-Won Park ,Soo Hyun Kim

doi:10.1371/journal.pone.0002594

Abstract

Aquaporins (AQPs) have previously been associated with increased expression in solid tumors. However, its expression in hematologic malignancies including CML has not been described yet. Here, we report the expression of AQP5 in CML cells by RT-PCR and immunohistochemistry. While normal bone marrow biopsy samples (n = 5) showed no expression of AQP5, 32% of CML patient samples (n = 41) demonstrated AQP5 expression. In addition, AQP5 expression level increased with the emergence of imatinib mesylate resistance in paired samples (p = 0.047). We have found that the overexpression of AQP5 in K562 cells resulted in increased cell proliferation. In addition, small interfering RNA (siRNA) targeting AQP5 reduced the cell proliferation rate in both K562 and LAMA84 CML cells. Moreover, by immunoblotting and flow cytometry, we show that phosphorylation of BCR-ABL1 is increased in AQP5-overexpressing CML cells and decreased in AQP5 siRNA-treated CML cells. Interestingly, caspase9 activity increased in AQP5 siRNA-treated cells. Finally, FISH showed no evidence of AQP5 gene amplification in CML from bone marrow. In summary, we report for the first time that AQP5 is overexpressed in CML cells and plays a role in promoting cell proliferation and inhibiting apoptosis. Furthermore, our findings may provide the basis for a novel CML therapy targeting AQP5.

Highlights

Aquaporins (AQPs) are water channel proteins that facilitate transcellular water movements [1,2]
AQP type 5 (AQP5) is expressed in human Chronic Myelogenous Leukemia (CML) cells First, we studied the expression profile of AQP5 in leukemic cell lines as well as CML primary cells
With RT-polymerase chain reaction (PCR) analysis, K562, EM-2, and LAMA-84 human CML cell lines and U937 human monoblastic leukemia cell line showed a clear expression of AQP5 (Figure 1A)

Summary

Introduction

Aquaporins (AQPs) are water channel proteins that facilitate transcellular water movements [1,2]. Each of the ten known human AQPs has a unique expression pattern [1]. The ectopic expression of human AQPs has been reported to be frequently associated with various cancers. AQP1 is expressed in brain [8], colon [9], and pancreatic cancers [6] and the microvessels in multiple myeloma [10], AQP3 in renal cell carcinoma [11] and AQP5 in colon [9], pancreatic [6], and ovarian cancers [12]. We have previously reported that AQP5 expression is associated with an early stage of colorectal cancer development. The expression of human AQP1, AQP3, and AQP5 was detected in tumor-infiltrating lymphocytes surrounding bronchogenic cancer of lung [13]

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Results

Conclusion